6533b874fe1ef96bd12d631c
RESEARCH PRODUCT
A Versatile Approach to CF3-Containing 2-Pyrrolidones by Tandem Michael Addition-Cyclization: Exemplification in the Synthesis of Amidine Class BACE1 Inhibitors
Myriam CiordiaMyriam CiordiaAndrés A. TrabancoMaría Sánchez-rosellóGary TresadernMichiel Van GoolNatalia MateuLaura Pérez-benitoSantos FusteroOscar Delgadosubject
Hydrocarbons FluorinatedMolecular StructureTandemAmino estersDrug discoveryStereochemistryOrganic ChemistryAmidinesStereoisomerismSequence (biology)General ChemistryCombinatorial chemistryPyrrolidinonesCatalysisStereocenterAmidinechemistry.chemical_compoundchemistryCyclizationBiological propertyDrug DiscoveryMichael reactionAspartic Acid EndopeptidasesAmyloid Precursor Protein Secretasesdescription
The synthesis of new fluorinated pyrrolidones starting from unprotected amino esters and amino nitriles through a Michael addition-lactamization sequence is described. The resulting CF3 -containing building blocks, bearing a quaternary stereogenic center adjacent to the fluorinated group, have been converted into amino pyrrolidines that display potent β-secretase 1 (BACE1) inhibitory activity. This work constitutes an example of selective fluorination as a valid strategy for the modulation of physicochemical and biological properties of lead compounds in drug discovery.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-04-28 | Chemistry - A European Journal |